Design and Synthesis of Quinazolinone-Triazole Hybrids as Potent Anti-Tubercular Agents.

A straightforward and convenient methodology has been developed for the reaction of 2-aminobenzamide and carbonyls affording 2,3-dihydroquinazolin-4(1H)-ones using aqueous solution of [C12Py][FeCl3Br]. The developed methodology was applied for the synthesis of 25 quinazolinone-triazole hybrids followed by evaluation of their in vitro anti-tubercular (TB) activity. The results revealed that 8 quinazolinone-triazole hybrids displayed promising activity having MIC values of 0.78-12.5 µg/mL. The compound 3if with MIC 0.78 µg/mL was found to be the lead nominee among the series, better than Ethambutol, a first line anti-TB drug and comparable with Rifampicin. The active compounds with MIC values ≤ 6.25 µg/mL were subjected to in vitro cytotoxicity and found nontoxic. In drug-drug interaction, compounds 3ia and 3ii interacted synergistically with all the three anti-TB drugs, INH, RFM, and EMB. Other 3 compounds interacted either in synergistic or additive manners. Important information on the binding interaction of the target compounds with the active sites of 1DQY Antigen 85C from Mycobacterium tuberculosis and Enoyl acyl carrier protein reductase (InhA) enzymes was obtained from molecular docking studies. Screening of the drug-likeness properties and bioactivity score indicates that synthesized molecules could be projected as potential drug candidates. Based on the current study, quinazolinone-triazole hybrids framework can be useful in drug development for TB.

Species Composition and Diversity Dynamics of Actinomycetes in Arid and Semi-arid Salt Basins of Rajasthan.

Species composition and diversity dynamics of the actinomycetes was studied in five salt basins of arid and semi-arid areas of Rajasthan, India. A novel approach integrating molecular (16S rRNA gene) and diversity indices was applied to reveal species composition and diversity dynamics. Fifty-three actinomycetes isolates were isolated from five arid and semi-arid salt basins. Molecular characterization resulted in the identification of actinomycetes species belonging to three genera namely, Streptomyces, Nocardiopsis, and Actinoalloteichus. The diversity study among actinomycetes species validates their universal occurrence in arid and semi-arid regions of Rajasthan. The species N. dassonvillei subsp. albirubida was omnipresent in all the five salt basins but its relative manifestation was not static across habitats. The study revealed that three species N. chromatogenes, S. durbertensis, and S. mangrovicola are being reported for the first time from India. The maximum species of actinomycetes were recorded from Pachpadra (14) and the minimum from Didwana area (6). This study not only documents the hitherto wealth of actinomycetes species in arid and semi-arid salt basins of Rajasthan but also reveals the composition and diversity dynamics of actinomycetes.

In-Silico Validation of Prosopis ciniraria Therapeutic Peptides Against Fungal Cell Wall: Better Treatment Strategy for Fungal Diseases.

Prosopis cineraria commonly known as Druce are valuable herb that holds antibacterial role, antifungal properties. We identified different peptides from this plant by deploying CADD (Computer-aided-drug-designing) approaches, these peptide sequences are as follows seq1 (RHDEEEEKAKV),seq3(KSNSTVEISQNVQSVDSSKM),seq4(KQVAEMNKPAVGSKTSDANHDLKS),seq5(KTKSAGNDSIQSTKPVPSALTVDKA),seq6(RELEDSNIHHVAASVVLESKSSRT), and seq8(LYSKVELHPFGLHNLGNSCYANAVFSV), these peptides holds therapeutic properties as shows interaction with chitin, a major constituent of fungal cell wall. Molecular docking was conducted by using AutoDock-Vina tool and the results were found to be promising where all binding energies were found in the range of - 9.1 to - 7.5 kcal/mol, it indicates strong binding of peptide sequences with chitin molecule. Even the toxicity analysis supports the considered peptide sequences to hold therapeutic role against fungus with non-toxic effect on humans. These peptides were successfully predicted as important therapeutic agents of P. cinerariaseed that can initiate chitin breakdown, due to their possible strong interaction with fungal cell wall and it also suggests this medicinal plant holds the key for multiple fungal disease treatments. This study will open new research dimensions and integration of computational biology with microbial pathology that will assist scientific and medical community to develop rapid disease prevention strategies against fungal pathogenesis.

Actinomycetes isolates of arid zone of Indian Thar Desert and efficacy of their bioactive compounds against human pathogenic bacteria.

Twenty-six morphotypes of actinomycetes bacteria were isolated from the soils of arid zone of Indian Thar desert, Rajasthan. A significant and positive correlation was found between density of actinomycetes isolates and availability of nitrogen in sandy soil of arid zone suggesting the influence of soil nitrogen on occurrence and propagation of actinomycetes in this region. Molecular identification based on 16S rRNA gene sequencing revealed that the bacterial isolates belong to four actinomycetes genera, viz. Streptomyces (22 species), Nocardiopsis (two species), Saccharomonospora (one species) and Actinoalloteichus (one species). The preliminary screening of 26 isolates against five human pathogenic bacteria, viz. Escherichia coli, Vibrio cholera, Salmonella enterica typhimurium, Staphylococcus aureus and Enterococcus faecalis, showed that only four isolates, viz. Streptomyces sp. (ITD-27), S. enissocaesilis (ITD-29), S. Malachitospinus (ITD-35) and Streptomyces sp. (ITD-47), had antibacterial activity. The secondary screening of these four isolates revealed that the isolate S. malachitospinus (ITD-35) showed the maximum growth inhibition zone and inhibited the growth of all tested gram-positive and gram-negative pathogenic bacteria. Gas chromatography-mass spectrometry analysis of S. malachitospinus (ITD-35) cultural filtrate in n-butanol solvent identified three antibacterial compounds of medicinal significance, viz. 3-octanone, neopentyl isothiocyanate and 2-methyl butyl isothiocyanate.

Magnetic proline-based ionic liquid surfactant as a nano-carrier for hydrophobic drug delivery.

Magnetic proline-based surface-active ionic liquid ([ProC10][FeCl3Br]) have been synthesized and investigated for their application in hydrophobic drug delivery. Hydrophobic drugs lead to poor absorptivity, drug aggregation, and high local toxicity. Herein, the vesicular structures formed from [ProC10][FeCl3Br] have been used as drug delivery reactors. The self-assembly behavior of [ProC10][FeCl3Br] in aqueous medium has been investigated using tensiometry, fluorescence, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The physicochemical interactions of [ProC10][FeCl3Br] with animal DNA have been studied using circular dichroism (CD), fluorescence, zeta potential, and gel electrophoresis to confirm its bio-friendly nature. The engendered vesicles prepared from [ProC10][FeCl3Br] have been investigated for the in vitro drug delivery of guest molecule pyrene as a hydrophobic model drug and ciprofloxacin as a hydrophobic antibiotic drug. The drug loading capacity and spontaneous kinetic release of the drug have been studied using various theoretical mathematical drug release models.

Synthesis and biological evaluation of novel 1,2,3-triazole derivatives as anti-tubercular agents.

A library of seventeen novel 1,2,3-triazole derivatives were efficiently synthesized in excellent yields by the popular 'click chemistry' approach and evaluated in vitro for their anti-tubercular activity against Mycobacterium tuberculosis H37Ra (ATCC 25177 strain). Among the series, six compounds exhibited significant activity with minimum inhibitory concentration (MIC) values ranging from 3.12 to 0.78µg/mL and along with no significant cytotoxicity against MBMDMQs (mouse bone marrow derived macrophages). Molecular docking of the target compounds into the active site of DprE1 (Decaprenylphosphoryl-ß-d-ribose-2'-epimerase) enzyme revealed noteworthy information on the plausible binding interactions.

Surface-Active Ionic Liquid Cholinium Dodecylbenzenesulfonate: Self-Assembling Behavior and Interaction with Cellulase.

The conventional sodium dodecylbenzenesulfonate (NaDBS) has been converted into an efficient and nontoxic anionic surface-active ionic liquid, cholinium dodecylbenzenesulfonate (Cho[DBS]). We have investigated its self-assembling behavior, interaction with the enzyme cellulase, and ecotoxicity. The surface-active properties at the air-liquid interface and the aggregation behavior of Cho[DBS] in water have been determined using tensiometry, isothermal titration calorimetry (ITC), conductometry, and dynamic light scattering (DLS). The enzyme activity was observed using dinitro salicylic acid analysis. The enhanced enzyme activity was explained through active-site exfoliation and structural constancy of cellulase in the micellar medium using the results from fluorescence, circular dichroism, DLS, and ITC. The nontoxic nature was confirmed by toxicity analysis on the freshwater microalgae Scenedesmus sp.

Illuminating microemulsions: ionic liquid-CdS quantum dots hybrid materials as potential white light harvesting systems.

Microemulsions (MEs) comprising of 2-hydroxyethylammonium formate, (HO-EAF), isooctane and dioctylsulfosuccinate proliniumisopropylester ([ProC3]AOT) have been constructed and used to prepare and stabilize CdS Quantum Dots (QDs) at room temperature. Such hybrid materials exhibited tunable light emission wherein the photoluminescence chromaticity could be precisely adjusted to pure white with a quantum efficiency (QE) of ∼43%, by adjusting the droplet size of MEs.

Synergistic effects of Arbuscular mycorrhizal fungi and plant growth promoting rhizobacteria in bioremediation of iron contaminated soils.

Three Arbuscular mycorrhizal fungi (AMF) from Glomus, Acaulospora and Scutellospora, and four plant growth promoting rhizobacteria (PGPR) isolates related to genera Streptomyces, Azotobacter, Pseudomonas and Paenibacillus were found to be effective in phytoremediation of Fe(3+) contaminated soil where Pennisetum glaucum and Sorghum bicolor were growing as host plants. Co-inoculation of AMF and PGPR showed better results in comparison to either, AMF and PGPR under pot conditions. Both AMF and PGPR were able to produce siderophores. AMF and PGPR associated to P. glaucum and S. bicolor plants increased the extent of iron absorption. AMF and PGPR combination exhibited superior (p < 0.01) phytoremediation efficiency with P. glaucum compared to S. bicolor. These findings warrant further investigations of these synergistic interactions and large-scale in situ studies for bioremediation of iron-contaminated soils.

Occurrence and characterization of hitherto unknown Streptomyces species in semi-arid soils.

Streptomyces the predominant genus of Actinobacteria and plays an important role in the recycling of soil organic matter and production of important secondary metabolites. The occurrence and diversity assessment of Streptomyces species revealed alkaline and poor nutrient status of soils of semi-arid region of Jodhpur, Rajasthan. The morphological and biochemical characterization of 21 Streptomyces isolates facilitated Genus level identification but were insufficient to designate species. Species designation based on 16S rRNA gene delineated 21 isolates into 14 Streptomyces species. Upon BLAST search, the test isolates exhibited 98 to 100% identities with that of the best aligned sequences of the NCBI database. The GC content of 16S rRNA gene sequences of all the Streptomyces isolates tested ranged from 59.03% to 60.94%. The multiple sequence alignment of all the 21 Streptomyces isolates generated a phylogram with high bootstrap values indicating reliable grouping of isolates based on nucleotide sequence variations by way of insertion, deletion and substitutions and 16S rRNA length polymorphism. Some of the Streptomyces species molecularly identified under present study are reported for the first time from semi-arid region of Jodhpur.

Spontaneous Formation of Multiarchitecture Vesicles of [C8mim]Br + [Na]DBS in Aqueous Medium: Synergic Interplay of Electrostatic, Hydrophobic, and π-π Stacking Interactions.

A mixture of a cationic surface active ionic liquid, [C8mim]Br and anionic surfactant, [Na]DBS has been shown to form unilamellar vesicles in water over an exceptionally wide mole fraction range of [C8mim]Br (x1 = 0.2 to 0.8). Formation of vesicles has been evidenced from transmission electron microscopy (TEM), cryo-TEM and atomic force microscopy (AFM) imaging. Cryo-TEM imaging of an equimolar mixture showed multiarchitectural unilamellar vesicles (spherical, tubular, and ribbon). Such complex architectures were earlier reported for Janus dendrimers of different structures (Science, 2010, 328, 1014). The synergism between oppositely charged single chain surfactants to form bilayer structures has been explained based on the evidence of π-π stacking interaction from 2D NOESY measurements, Coulombic interactions from zeta potential measurements and magnitude of interaction parameter from the critical aggregation concentration. The aggregation concentrations were measured from tensiometry and fluorescence using pyrene as a polarity probe. The phase behavior at different mixture compositions has been revealed from turbidity measurements and visual inspection. Hydrodynamic radii of self-assembled structures in the bulk solution phase were measured from dynamic light scattering. Vesicles formed have been explored as delivery vehicles for proteins using bovine serum albumin (BSA) as model.

Sodium bromide induced micelle to vesicle transitions of newly synthesized anionic surface active ionic liquids based on dodecylbenzenesulfonate.

Dodecylbenezenesulfonate-based anionic surface active ionic liquids (DBS-ILs) paired with onium cations, n-butyltrimethylammonium ([N1114]), 1-butyl-3-methylimidazolium ([C4mim]), and N-butylpyridinium ([C4Py]) have been synthesized. DBS-ILs were found to be highly surface active having critical micelle concentration (CMC) lower than that of their conventional analogue sodium dodecylbenezenesulfonate ([Na][DBS]). The CMC values of DBS-ILs were determined from surface tension (ST) and isothermal titration calorimetry (ITC). DBS-ILs formed micelles predominantly in the aqueous medium, and unlike [Na]DBS, the micelles of DBS-ILs could be transformed into vesicles with the addition of sodium bromide (NaBr). Micelle to vesicle transitions (MVTs) were evidenced from dynamic light scattering (DLS), turbidity, proton nuclear magnetic resonance ((1)H NMR), and cryo-TEM techniques. Thermodynamics of aggregation was investigated from ITC which indicated that the aggregation process is primarily driven by the entropy factor. The formation of a vesicle upon addition of NaBr has been accounted to the increased electrostatic interactions between the less hydrated sulfonate headgroup and the more populated bigger sized counterions along with the favored cation-π or π-π interactions between them as evidenced from 2D-NOESY NMR experiments. The stimuli-responsive morphological transitions in the self-assembly of the reported anionic surface active ionic liquids (SAILs) will be useful for encapsulation and delivery of active (bio)molecules in the targeted biomedical applications.

Temperature-dependent solubility transition of Na2SO4 in water and the effect of NaCl therein: solution structures and salt water dynamics.

Dual, aqueous solubility behavior of Na2SO4 as a function of temperatures is still a natural enigma lying unresolved in the literature. The solubility of Na2SO4 increases up to 32.38 °C and decreases slightly thereafter at higher temperatures. We have thrown light on this phenomenon by analyzing the Na2SO4-water clusters (growth and stability) detected from temperature-dependent dynamic light scattering experiments, solution compressibility changes derived from the density and speed of sound measurements, and water structural changes/Na2SO4 (ion pair)-water interactions observed from the FT-IR and 2D DOSY (1)H NMR spectroscopic investigations. It has been observed that Na2SO4-water clusters grow with an increase in Na2SO4 concentration (until the solubility transition temperature) and then start decreasing afterward. An unusual decrease in cluster size and solution compressibility has been observed with the rise in temperature for the Na2SO4 saturated solutions below the solubility transition temperature, whereas an inverse pattern is followed thereafter. DOSY experiments have indicated different types of water cluster species in saturated solutions at different temperatures with varying self-diffusion coefficients. The effect of NaCl (5-15 wt %) on the solubility behavior of Na2SO4 at different temperatures has also been examined. The studies are important from both fundamental and industrial application points of view, for example, toward the clean separation of NaCl and Na2SO4 from the effluent streams of textile and tannery industries.

Self-assembly of new surface active ionic liquids based on Aerosol-OT in aqueous media.

New anionic ionic liquid surfactants have been synthesized by replacing the sodium cation of Aerosol-OT (sodium dioctylsulfosuccinate, [Na]AOT) with various biocompatible moieties, such as 1-butyl-3-methyl imidazolium ([C4mim]), proliniumisopropylester ([ProC3]), cholinium ([Cho]), and guanidinium ([Gua]). The Aerosol-OT derived ionic liquids (AOT-ILs) were found fairly soluble in water and formed vesicles above a critical vesicle concentration (CVC) which depended upon the nature of cation, and followed the order: [ProC3]<[C4mim]<[Gua]<[Cho]

Morphometric and molecular characterization of fungus Pestalotiopsis using nuclear ribosomal DNA analysis.

Taxonomy of the fungus Pestalotiopsis based on morphological characters has been equivocal. Molecular characterization often Pestalotiopsis species was done based on nuclear ribosomal DNA internal transcribed spacer (ITS) amplifications. Results of the analyses showed that species of genus Pestalotiopsis are monophyletic. We report ITS length variations, single nucleotide polymorphisms (SNPs) and insertions/ deletions (INDELS) among ten species of Pestalotiopsis that did not cause any phylogenetic error at either genus or species designation levels. New gene sequences have been assigned (Gen Accession numbers from HM 190146 to HM 190155) by the National Centre for Biotechnology Information, USA.